Sexually transmitted diseases (STDs) are of major medical and social importance worldwide, affecting about[unreadable] 500 million people annually, with debilitating or life-threatening consequences. Genital infections caused by[unreadable] Chlamydia trachomatis and Herpes simplex virus type 2 (HSV-2) rank among the highest STDs in the world.[unreadable] Genital chlamydial infection is the most common bacterial STD in the United States with severe irreversible[unreadable] complications in women, including pelvic inflammatory disease, fallopian tube scarring, ectopic pregnancy[unreadable] and infertility. Four million reported annual cases involve over $2 billion in treatment cost. Genital herpes is a[unreadable] widespread STD with severe complications, especially in neonates and immunocompromised individuals,[unreadable] including neonatal herpes and central nervous system involvement. Of the current control and prevention[unreadable] strategies, including early detection and treatment, vaccines capable of protecting against infection or severe[unreadable] disease would be the most effective long-term option to control diseases due to Chlamydia and HSV-2. A[unreadable] vaccine offers the best approach to protect the greatest number of people against infection. There is currently[unreadable] no licensed vaccine against either Chlamydia or herpes infections. Considering the high incidence of coinfections[unreadable] by both C. trachomatis and HSV-2, the availability of a combination vaccine that can be[unreadable] administered as a single regimen to protect against multiple infections would be highly desirable. Efficacious[unreadable] vaccines against Chlamydia and genital herpes would require identification of appropriate antigens and[unreadable] development of effective delivery vehicles capable of eliciting long-lasting protective immunity. We have[unreadable] designed a novel recombinant bacterial ghost delivery system which has inherent adjuvant properties and[unreadable] capable of simultaneously delivering multiple antigens from the same or different pathogens to the immune[unreadable] system. This proposal describes the use of the novel recombinant Vibrio cholerae ghost (rVCG) technology[unreadable] to develop a multivalent subunit combination vaccine comprising select outer membrane proteins (OMPs)[unreadable] including the highly immunogenic major OMP (MOMP) and PorB of C. trachomatis and the glycoprotein D[unreadable] (gD2) and B (gB2) of HSV-2. The hypothesis to be investigated is that immunization with a multivalent[unreadable] combination vaccine composed of rVCG expressing subunit antigens from both Chlamydia and HSV-[unreadable] 2 will simultaneously induce protective immunity against both genital Chlamydia and herpes[unreadable] infections. We have chosen MOMP, PorB, gD2 and gB2 as appropriate immunogens since these antigens[unreadable] contain protective T cell and neutralizing epitopes. Our aims are to: (a) genetically design an rVCG vectorbased[unreadable] multivalent subunit combination vaccine, and (b) assess the immunogenicity and protective efficacy of[unreadable] this vaccine construct in an appropriate animal model. Results from these studies will likely lead to the[unreadable] development of a reliable combination vaccine regimen against Chlamydia and HSV-2, which should have[unreadable] major implications for the control of STDs and their complications.